Brain-Printing Biometrics underlying mechanism as an early diagnostic technique for Alzheimer's disease neurodegenerative type

AbstractThough sleep disturbance constitutes the risk factor for Alzheimer’s disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.

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P2-176: Are cortical sources of auditory oddball event-related potentials an early diagnostic marker of Alzheimer's disease?

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.06.715 ◽

2015 ◽

Vol 11 (7S_Part_12) ◽

pp. P559-P559

Author(s):

Claudio Babiloni ◽

Claudio Del Percio ◽

Nicola Marzano ◽

Susanna Cordone ◽

Giuseppe Noce ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diagnostic Marker ◽

Event Related Potentials ◽

Auditory Oddball ◽

Cortical Sources ◽

Related Potentials ◽

Early Diagnostic

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Longitudinal data in peripheral blood confirm that PM20D1 is a quantitative trait locus (QTL) for Alzheimer’s disease and implicate its dynamic role in disease progression

Clinical Epigenetics ◽

10.1186/s13148-020-00984-5 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Qi Wang ◽

Yinghua Chen ◽

Benjamin Readhead ◽

Kewei Chen ◽

Yi Su ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dna Methylation ◽

Longitudinal Data ◽

Disease Progression ◽

Peripheral Blood ◽

Early Stage ◽

Underlying Mechanism ◽

Methylation Data ◽

Brain Tissues

Abstract Background While Alzheimer’s disease (AD) remains one of the most challenging diseases to tackle, genome-wide genetic/epigenetic studies reveal many disease-associated risk loci, which sheds new light onto disease heritability, provides novel insights to understand its underlying mechanism and potentially offers easily measurable biomarkers for early diagnosis and intervention. Methods We analyzed whole-genome DNA methylation data collected from peripheral blood in a cohort (n = 649) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and compared the DNA methylation level at baseline among participants diagnosed with AD (n = 87), mild cognitive impairment (MCI, n = 175) and normal controls (n = 162), to identify differentially methylated regions (DMRs). We also leveraged up to 4 years of longitudinal DNA methylation data, sampled at approximately 1 year intervals to model alterations in methylation levels at DMRs to delineate methylation changes associated with aging and disease progression, by linear mixed-effects (LME) modeling for the unchanged diagnosis groups (AD, MCI and control, respectively) and U-shape testing for those with changed diagnosis (converters). Results When compared with controls, patients with MCI consistently displayed promoter hypomethylation at methylation QTL (mQTL) gene locus PM20D1. This promoter hypomethylation was even more prominent in patients with mild to moderate AD. This is in stark contrast with previously reported hypermethylation in hippocampal and frontal cortex brain tissues in patients with advanced-stage AD at this locus. From longitudinal data, we show that initial promoter hypomethylation of PM20D1 during MCI and early stage AD is reversed to eventual promoter hypermethylation in late stage AD, which helps to complete a fuller picture of methylation dynamics. We also confirm this observation in an independent cohort from the Religious Orders Study and Memory and Aging Project (ROSMAP) Study using DNA methylation and gene expression data from brain tissues as neuropathological staging (Braak score) advances. Conclusions Our results confirm that PM20D1 is an mQTL in AD and demonstrate that it plays a dynamic role at different stages of the disease. Further in-depth study is thus warranted to fully decipher its role in the evolution of AD and potentially explore its utility as a blood-based biomarker for AD.

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Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8340192 ◽

2019 ◽

Vol 2019 ◽

pp. 1-27 ◽

Cited By ~ 1

Author(s):

Yan Liu ◽

Ting Du ◽

Wenlong Zhang ◽

Weiye Lu ◽

Zhichao Peng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Underlying Mechanism ◽

Therapeutic Drug ◽

Glutamatergic Transmission ◽

Chinese Herbal Formula ◽

Microbiome Analysis ◽

Chinese Herbal ◽

Model Of Alzheimer’S Disease ◽

Tof Ms

Alzheimer’s disease (AD) is a common neurodegenerative disease, characterized by cognitive dysfunction; however, the therapeutic strategies are not fully understood. Huang-Lian-Jie-Du-Decoction (HLJDD) is a famous traditional Chinese herbal formula that has been widely used clinically to treat dementia. Recently, according to previous study and our clinical practice, we generate a new modification of HLJDD (named modified-HLJDD). In this study, we indicated that modified-HLJDD attenuated learning and memory deficiencies in Aβ1-42 oligomer-induced AD model, and we confirmed the exact metabolites in modified-HLJDD solution, as compared with HLJDD by UHPLC-Q-TOF-MS. Using GC-Q-TOF/MS-based metabolomics, we identified adenosine as the potential significant metabolite, responsible for modified-HLJDD regulating energy metabolism and synaptic plasticity in AD model. We also revealed that the potential underlying mechanism of modified-HLJDD in AD model may involve NMDA receptor-mediated glutamatergic transmission and adenosine/ATPase/AMPK cascade. Moreover, we also indicated the differential gut microbiota which mainly involved Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level upon modified-HLJDD treatment in AD model. Based on the correlation of metabolomic analysis with microbiome analysis, we clarified that Dorea is the most affected microbiota with adenosine upon modified-HLJDD treatment in AD model. Thus, our study suggests that modified-HLJDD may serve as a potential therapeutic drug in treating AD.

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BHARAT: An Integrated Big Data Analytic Model for Early Diagnostic Biomarker of Alzheimer's Disease

Frontiers in Neurology ◽

10.3389/fneur.2019.00009 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 4

Author(s):

Ankita Sharma ◽

Deepika Shukla ◽

Tripti Goel ◽

Pravat Kumar Mandal

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Big Data ◽

Analytic Model ◽

Diagnostic Biomarker ◽

Data Analytic ◽

Early Diagnostic

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THE APOE-ε4 ALLELE AND AGE SYNERGISTICALLY DRIVE DISEASE PROGRESSION IN ALZHEIMER’S DISEASE

Innovation in Aging ◽

10.1093/geroni/igz038.3427 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S943-S943

Author(s):

Luca Kleineidam ◽

Andrea R Zammit ◽

Alyssa DeVito ◽

Richard B Lipton ◽

Oliver Peters ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Progression ◽

Underlying Mechanism ◽

Additive Models ◽

Tau Pathology ◽

Case Control Studies ◽

Cross Sectional ◽

Apoe Ε4 ◽

Ε4 Allele

Abstract The Apolipoprotein E (APOE)-ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD) and other neurodegenerative dementias. Cross-sectional case-control studies suggest that the effect of APOE-ε4 decreases in old age. However, since APOE- ε4 is associated with mortality, these studies might be prone to bias due to selective survival. Therefore, we used multi-state-modeling in longitudinal cohort studies to examine the effect of APOE-ε4 on the transition through cognitive states (i.e. cognitively normal, mild cognitive impairment (MCI) and dementia) while taking death as a competing risk into account. Results from the German AgeCoDe study (n=3000, aged 75-101 years) showed that APOE-ε4 increases the risk for cognitive deterioration in all disease stages. Contrary to results from cross-sectional studies, the effect of APOE-ε4 on the transition from MCI to dementia increased with increasing age (HR=1.044, 95%-CI=1.001-1090). The direction of this effect was confirmed in a smaller sample from the Einstein Aging Study (n=744, HR=1.032, 95%-CI=0.949-1.122). To examine the pathophysiological basis of these results, generalized additive models were used to study AD biomarkers in the liquor of 1045 patients with MCI or AD-dementia. Here, increased amyloid (Abeta1-42) pathology was associated with increased tau pathology (pTau181), consistent with the amyloid-cascade-hypothesis. Interestingly, higher age and presence of the APOE-ε4 synergistically lowered the amount of amyloid required to exacerbate tau pathology (interaction p=0.012). Taken together, our results suggest that the effect of APOE-ε4 on disease progression increases with advancing age. An altered neuroinflammatory response to neurodegeneration should be further explored as potential underlying mechanism.

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APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids

Nature Communications ◽

10.1038/s41467-020-19264-0 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Jing Zhao ◽

Yuan Fu ◽

Yu Yamazaki ◽

Yingxue Ren ◽

Mary D. Davis ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Subject ◽

Late Onset ◽

Disease Patient ◽

Underlying Mechanism ◽

Synapse Loss ◽

Induced Pluripotent ◽

Human Ipsc ◽

Normal Cognition

Abstract APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype from individuals with either normal cognition or AD dementia. Cerebral organoids from AD patients carrying APOE ε4/ε4 show greater apoptosis and decreased synaptic integrity. While AD patient-derived cerebral organoids have increased levels of Aβ and phosphorylated tau compared to healthy subject-derived cerebral organoids, APOE4 exacerbates tau pathology in both healthy subject-derived and AD patient-derived organoids. Transcriptomics analysis by RNA-sequencing reveals that cerebral organoids from AD patients are associated with an enhancement of stress granules and disrupted RNA metabolism. Importantly, isogenic conversion of APOE4 to APOE3 attenuates the APOE4-related phenotypes in cerebral organoids from AD patients. Together, our study using human iPSC-organoids recapitulates APOE4-related phenotypes and suggests APOE4-related degenerative pathways contributing to AD pathogenesis.

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Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21176419 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6419

Author(s):

Jong Youl Kim ◽

Sumit Barua ◽

Ye Jun Jeong ◽

Jong Eun Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Underlying Mechanism ◽

Mechanistic Studies ◽

Beneficial Effects ◽

Adipose Tissue Dysfunction ◽

Insulin Receptor Signaling ◽

Receptor Signaling Pathway ◽

Ad Prevention ◽

Safe Approach

Animal and human mechanistic studies have consistently shown an association between obesity and Alzheimer’s disease (AD). AD, a degenerative brain disease, is the most common cause of dementia and is characterized by the presence of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles disposition. Some studies have recently demonstrated that Aβ and tau cannot fully explain the pathophysiological development of AD and that metabolic disease factors, such as insulin, adiponectin, and antioxidants, are important for the sporadic onset of nongenetic AD. Obesity prevention and treatment can be an efficacious and safe approach to AD prevention. Adiponectin is a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation. It has been shown to be inversely correlated with adipose tissue dysfunction and may enhance the risk of AD because a range of neuroprotection adiponectin mechanisms is related to AD pathology alleviation. In this study, we summarize the recent progress that addresses the beneficial effects and potential mechanisms of adiponectin in AD. Furthermore, we review recent studies on the diverse medications of adiponectin that could possibly be related to AD treatment, with a focus on their association with adiponectin. A better understanding of the neuroprotection roles of adiponectin will help clarify the precise underlying mechanism of AD development and progression.

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Olfactory dysfunction in Alzheimer’s disease Systematic review and meta-analysis

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn12-020004 ◽

2018 ◽

Vol 12 (2) ◽

pp. 123-132 ◽

Cited By ~ 21

Author(s):

Maren de Moraes e Silva ◽

Pilar Bueno Siqueira Mercer ◽

Maria Carolina Zavagna Witt ◽

Renata Ramina Pessoa

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Diagnosis ◽

Effect Size ◽

Meta Analysis ◽

Olfactory Dysfunction ◽

Diagnostic Evaluation ◽

Olfactory Analysis ◽

Early Diagnostic

Abstract Alzheimer’s disease (AD), a neurodegenerative condition, is one of the most prevalent kinds of dementia, whose frequency doubles for every 5 years of age in elderly. Objective: To determine the correlation between AD and olfactory alterations, identifying the most affected domains and exploring the utility of olfactory tests for complementing early diagnosis. Methods: Databases were searched using the terms “olfactory OR smell OR olfaction AND alzheimer” for articles related to the proposed theme. The selected studies were categorized and evaluated separately depending on the method of analysis of the olfactory tests: identification of odors, discrimination and recognition, and a meta-analysis was carried out. Results: Fifty-one articles were selected for analysis. The effect size for most studies was large, as were the summary values for each category of individualized olfactory analysis. Conclusion: Among the olfactory domains, except memory, identification appears to be the most altered in AD. The possibility of including tests that specifically evaluate the identification of odors as an item in early diagnostic evaluation should be explored. PROSPERO registration: CRD42018089076.

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